Although bisphosphonates have been suggested to protect against atherosclerotic cardiovascular (CV) events, due to their ability to reduce calcification in arterial walls, evidence is still conflicting. We aimed to investigate the effect of bisphosphonates on CV outcomes.

We carried out a retrospective cohort study selecting from administrative databases of Lombardy (Italy) patients aged>40 years, with a first prescription of bisphosphonates between 2003/01/01 and 2006/12/31. Subjects were followed until the first CV event, death or migration, or 2012/12/31. Exposure to bisphosphonates was characterized based on cumulative doses (proportion of days covered). A proportional hazards model was fitted to estimate the association between cumulative time-dependent exposure to bisphosphonates and CV events (hazard ratios [HRs] and 95% confidence intervals). The model was adjusted for age, sex, comorbidities, and concomitant treatment at baseline.

Among 82,704 new bisphosphonates users (females 87.0%; mean age±SD 70.7±10.6 years), 16.1% experienced a CV event during the follow-up. Alendronic acid was the most commonly prescribed bisphosphonate (67.1%), followed by risedronic acid (22.1%). Compared with individuals with an exposure period≤40% of follow-up, those exposed for a period ranged between 41%-80% or more than 80% showed HRs of 0.95 [0.905-0.998] and 0.75 [0.706-0.805], respectively. Analogous trends were found stratifying for cardiovascular and cerebrovascular events (HRs 0.75 [0.682-0.825] and 0.76 [0.699-0.830], respectively).

These results suggested a strong CV risk reduction (ranged from 5% to 25%) with increasing number of days covered by bisphosphonate treatment. Further studies to confirm this protective effect of bisphosphonate therapy and to investigate possible underlying mechanisms are warranted.

02 - USE OF BISPHOSPHONATES AND RISK OF CARDIOVASCULAR EVENTS: A POPULATION-BASED RETROSPECTIVE COHORT STUDY